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D Vergani

Publications and source records attributed to D Vergani.

At least 55 records · Page 3Linked to original sources
PubMed1998

De-novo autoimmune hepatitis after liver transplantation.

BACKGROUND: Late graft dysfunction that does not result from recognised causes, such as rejection, infection, or vascular or biliary complications, can occur after liver transplantation. We investigated a particular type of unexplained graft dysfunction that is associated with autoimmune features in children who underwent transplantation at our unit between 1991 and 1996. METHODS: Seven (4%) of 180 liver-transplant recipients developed an unexplained but characteristic form of graft dysfunction (five boys, two girls; median age at presentation 10.3 years, range 2.0-19.4). The median period after surgery was 24 months (6-45). The indications for transplantation had been extrahepatic biliary atresia (four patients), Alagille's syndrome (one), drug-induced acute liver failure (one), and alpha1-antitrypsin deficiency (one). Four patients were on triple immunosuppression with cyclosporin, azathioprine, and prednisolone; and three were on tacrolimus. Immunoglobulin measurements, autoantibody studies, serological studies, and HLA typing were undertaken. Liver-biopsy samples were taken. FINDINGS: Infectious and surgical complications were excluded. Liver-biopsy samples showed the histological changes of chronic hepatitis, including portal and periportal hepatitis with lymphocytes and plasma cells, bridging collapse, and perivenular-cell necrosis without changes typical of acute or chronic rejection. All patients had high concentrations of IgG (median 22 g/L [range 17.2-34.4]) and high titres of autoantibodies. All but one patient responded to prednisolone 2 mg/kg daily and an increase in or addition of azathioprine (1.5 mg/kg daily) within a median of 32 days (7-316). One responder relapsed owing to poor compliance but went into remission after treatment was restored. All six respondents remain in remission on a reduced dose of prednisolone (5-10 mg/day) and 1.5 mg/kg daily azathioprine at a median of 283 days (range 108-730) follow-up. INTERPRETATION: Our data show that symptoms of autoimmune hepatitis, which are responsive to the classical treatment for this condition, can appear in liver-transplant patients while they are on anti-rejection immunosuppression. Whether the liver damage in these patients is a form of rejection or the consequence of autoimmune attack has yet to be established.

Anti-Inflammatory Agents↗
PubMed1998

MHC restriction to T-cell autoaggression: an emerging understanding of IDDM pathogenesis.

The Nobel prize-winning discovery of MHC restriction by Zinkernagel and Doherty has led to some of the most exciting advances in immunology over the past two decades. The ongoing progress in our conceptual understanding of the processes governing the immunology to infection, tolerance to self and consequently the immune dysregulation in autoimmunity have all assimilated the laws of restriction as a central tenet. The focus of much of this research has been the T-cell and its interactions. Refinement of the paradigm of MHC restriction at the molecular level has allowed a view of the pathogenesis of insulin-dependent diabetes mellitus (IDDM), a prototypic autoimmune disease, unprecedented in its detail. This article discusses the impact of MHC restriction on the central themes of immunology, and focuses on its utility as a framework in understanding the role of the T-cell in the pathogenesis of IDDM.

Animals↗
PubMed1998

Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis.

We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.

Amino Acid Sequence↗
PubMed1998

Cytokine overproduction in healthy first degree relatives of patients with IDDM.

Healthy family members of patients with insulin-dependent diabetes mellitus (IDDM) are known to share a number of immunological abnormalities with their affected relatives. Since monocyte and type 1 T-cell-derived cytokines contribute to the pathogenesis of IDDM, we studied the production of these cytokines in the healthy first degree relatives of 29 children with IDDM. We report that circulating tumour necrosis factor-alpha (TNF-alpha) and soluble interleukin-2 (sIL-2) receptor were present in increased amounts in non-diabetic family members at levels similar to those found in the diabetic children (duration of disease 3 months-5 years). Furthermore, marked hypersecretion of IL-1alpha and TNF-alpha by mitogen-stimulated peripheral blood mononuclear cells was found in both diabetic and healthy family members. Abnormalities of cytokine production in healthy relatives did not correlate with the presence of islet cell antibodies or with HLA DR type. These data indicate that healthy family members of patients with IDDM exhibit overproduction of a number of cytokines that have been implicated in diabetogenesis.

Adolescent↗
PubMed1998

Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection.

HCV infection and interferon-alpha (IFN-alpha) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-alpha cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-alpha, 22 untreated), tested on 165 occasions over a median of 9 months (range 5-42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-alpha had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-alpha; and (iii) IFN-alpha should be used cautiously in the treatment of LKM-1/HCV-positive patients.

Adolescent↗
PubMed1998

Argininosuccinate lyase: a new autoantigen in liver disease.

Anti-liver cytosol 1 autoantibody (LC1) characterizes a severe form of autoimmune hepatitis (AIH), staining the cytoplasm of periportal hepatocytes and targeting an unidentified 60-kD liver cytosolic antigen. To identify its target, we used high-titre anti-LCI+ sera from two patients with AIH to screen 18 cytoplasm enzymes with periportal location by double immunodiffusion (DDI). Both sera gave a broad precipitin line against human liver cytosol, suggesting that they may recognize two distinct antigens, a possibility confirmed by the appearance of two precipitin lines when DDI conditions were optimized (0.8% agarose and 3% polyethylene glycol (PEG)). Experiments by DDI and Western blot (WB) identified a liver cytosolic autoantigen of 50 kD, different from LC1, giving a line of identity with argininosuccinate lyase (ASL). Reactivity to ASL was then investigated by DDI and WB in 57 patients with AIH, 17 with primary biliary cirrhosis (PBC), 15 with chronic hepatitis B virus (HBV) infection, 13 with alphal-antitrypsin deficiency, 17 with Wilson's disease, 18 with extrahepatic autoimmune disorders, and in 48 healthy controls. Anti-ASL was found in 16% of AIH and 23% of PBC patients by DDI and in 14% of AIH, 23% of PBC and 20% of HBV patients by WB. No argininosuccinate was present in the urine of four anti-ASL+ patients tested, excluding an inhibition of enzymatic activity by anti-ASL. The addition of anti-ASL+ serum to human fibroblast cultures induced a significant increase in ASL activity. ASL is a new autoantigen in liver disease and its clinical relevance warrants further investigation.

Argininosuccinate Lyase↗
PubMed1998

Immunological liver diseases in children.

Autoimmune liver diseases comprise a number of disorders in which inflammatory damage to the liver is believed to derive from an autoimmune attack. These include autoimmune hepatitis (AIH), characterised by positive smooth muscle and/or nuclear (SMA/ANA) or liver kidney microsomal type 1 (LKM1) antibodies, autoimmune sclerosing cholangitis (ASC), usually SMA/ANA positive, and AIH after liver transplantation, which is positive for SMA, ANA, or atypical LKM. These disorders often present with symptoms indistinguishable from prolonged acute hepatitis. Less commonly the onset is insidious, with nonspecific symptoms, or with complications of portal hypertension. For AIH and ASC, experimental evidence suggests that usually in individuals genetically predisposed to autoimmunity, a liver self antigenic peptide is recognized by T lymphocytes which promote a cascade of autoaggressive processes. For AIH after liver transplantation, the pathogenic mechanisms remain to be elucidated. All types of autoimmune liver disorders appear to respond favourably to early treatment with prednisolone with or without azathioprine. For patients presenting with fulminant hepatic failure or with already advanced cirrhosis, immunosuppression is rarely effective and the only mode of treatment is liver transplantation. The role of other immunosuppressant or immunomodulatory drugs, like cyclosporin A, tacrolimus or ursodeoxycholic acid, in the treatment of autoimmune liver disorders remains to be defined.

Child↗
PubMed1998

Carcinoid heart disease from ovarian primary presenting with acute pericarditis and biventricular failure.

A case is described of a 54 year old woman who had acute pericarditis with large exudative effusion accompanied by severe right and left ventricular failure. The patient was finally diagnosed with carcinoid heart disease from an ovarian carcinoid teratoma. She was treated with octreotide--a somatostatin analogue--followed by radical surgical resection of the neoplasm. At one year follow up only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid heart disease from an ovarian primary have been described in literature. Moreover clinically manifest acute, nonmetastatic pericarditis and left heart failure are not considered as possible presentations of carcinoid heart disease, whatever the origin. In a recent series a small pericardial effusion was considered an infrequent and unexpected echocardiographic finding in carcinoid heart patients. One case of "carcinoid pericarditis" has previously been described as a consequence of pericardial metastasis. Left sided heart involvement is usually caused by bronchial carcinoids or patency of foramen ovale; both were excluded in the case presented.

Carcinoid Heart Disease↗
PubMed1997

Reproducibility and persistence of neural and adrenal autoantibodies in diabetic autonomic neuropathy.

The presence of autoantibodies to autonomic nervous tissue structures is a feature of patients with symptomatic diabetic autonomic neuropathy. It has not been established whether these autoantibodies cause, contribute to or simply reflect nervous tissue damage. Serum samples were tested for the presence of complement-fixing autoantibodies to adrenal medulla, vagus nerve, and sympathetic ganglion cells, to demonstrate: (a) reproducibility of the technique, (b) persistence of the antibodies, and (c) whether or not they occur in patients with non-insulin-dependent (Type 2) diabetes (NIDDM) with neuropathy. Examination of 37 samples, by different observers 2 years apart, revealed a high degree of concordance of both positive and negative results, demonstrating the method of testing to be highly reproducible. Re-testing of 37 patients (by analysing a second blood sample) between 0.5 and 2.7 years (mean 1.7 years) after their first test also demonstrated that antibodies, once present, normally persist; and that most patients initially negative remained so. Of 17 neuropathic NIDDM patients, 16 were negative for all three antibodies, indicating their rarity in this group of patients.

Adrenal Medulla↗
PubMed1997

Autoimmune hepatitis in childhood: a 20-year experience.

To determine the clinical, biochemical, and histological features, and outcome of childhood autoimmune hepatitis (AIH), we reviewed the medical records of 52 children with AIH, 32 (median age: 10 [2-15] years) anti-nuclear and/or smooth muscle antibody (ANA/SMA) positive, 20 (7 [0.8-14] years) liver/kidney microsomal antibody (LKM-1) positive, with median follow-up of 5 years (range 0.3-19). At presentation: 56% had symptoms of prolonged acute hepatitis; LKM-1 positive were younger (P = .011), with higher bilirubin (P = .007), and AST (P = .047); ANA/SMA positive had lower albumin (P = .023); 69% ANA/SMA positive, and 38% LKM-1 positive were cirrhotic (P = .080). ANA/SMA positive had increased frequency of HLA haplotype A1/B8/DR3/DR52a compared with controls (53% vs. 14%, P < .001). Of six (5 LKM-1 positive) with fulminant hepatitis, four were transplanted, one died, and one ANA/SMA positive improved with immunosuppression. Of 47 treated with immunosuppression, 2 (1 LKM-1 positive) died with no remission and 4 (2 LKM-1 positive) were transplanted 8 to 14 years after diagnosis. Immunosuppression was stopped successfully in 19% of ANA/SMA positive after a median of 3 years of treatment, but in none of LKM-1 positive. Baseline bilirubin and international normalized prothrombin ratio (INR) were independent variables predictive of outcome. In conclusion, ANA/SMA positive and LKM-1 positive AIH in childhood have clinical, biochemical, and histological differences, but similar severity and long-term outcome.

Adolescent↗
PubMed1997

Lymphocyte vaccination protects prediabetic non-obese diabetic mice from developing diabetes mellitus.

In the therapeutic manoeuvre termed "lymphocyte vaccination", activated lymphocytes capable of transferring an autoimmune disease are instead attenuated and given in vaccine form. We have previously shown that such a therapy administered to non-obese diabetic (NOD) mice at 6 weeks of age prevents diabetes mellitus. To assess whether this therapy has potential clinical relevance, in the present study lymphocyte vaccination was applied in NOD mice in 3 weekly doses commencing in the immediate prediabetic period (age 12 weeks), when insulitis is advanced and diabetes incipient. Of 30 NOD mice receiving active vaccine (composed of attenuated lymphocytes from diabetic NOD mice) 13 (43.3%) remained non-diabetic to the age of 30 weeks, in comparison with 2 of 30 (6.7%; p < 0.01) mice receiving a control vaccine (composed of attenuated lymphocytes from non-diabetic NOD/B10 mice) and 5 of 26 (19.2%; p < 0.01) mice receiving saline carrier alone. Moreover, in an additional group of 10 NOD mice receiving active vaccine weekly between 12 and 30 weeks, 8 remained diabetes free at the end of the treatment. The most notable effect of the vaccine was that the delay in diabetes onset was accompanied by a reduction in insulitis and in some cases a complete absence of infiltrating lymphocytes at 30 weeks of age. Immunocytochemistry indicated that when present, islet infiltrating lymphocytes in non-diabetic mice that received active vaccine showed significantly reduced staining for interferon-gamma, compared with the infiltrate seen in diabetic mice receiving the control vaccine or saline. This study demonstrates that the rapid progression to diabetes typically seen in 12-week-old NOD mice can be delayed by lymphocyte vaccination, supporting the possibility that a vaccine composed of attenuated autologous peripheral blood lymphocytes could be effective in high risk first degree relatives of patients with insulin dependent diabetes mellitus.

Animals↗
PubMed1997

Expression of glutamic acid decarboxylase in nervous tissue structures targeted by autoantibodies in patients with diabetic autonomic neuropathy.

We have previously identified an association between symptomatic diabetic autonomic neuropathy (DAN) and autoantibodies to sympathetic and parasympathetic nervous structures. The antigens identified by these autoantibodies are not known, but glutamic acid decarboxylase (GAD) has been suggested as a candidate target, since anti-GAD autoantibodies are present in patients with long-term diabetes and GAD is expressed in a variety of cell types and structures in the nervous system. The aim of this study was to examine GAD expression in sympathetic ganglia and vagus nerve and to compare the distribution of GAD within these tissues with that of anti-sympathetic ganglia and anti-vagus nerve autoantibodies from patients with DAN, using single and double indirect immunofluorescence on tissue sections. The monoclonal antibody GAD-6, specific for GAD65, gave a granular, peripheral, cytoplasmic staining pattern in sympathetic ganglion cells. Dual immunofluorescence demonstrated that serum from a patient with anti-sympathetic ganglion autoantibodies stained the same cells, but homogeneously throughout the cytoplasm. In the vagus nerve, patient's serum stained the fibres only; GAD-6 stained the cytoplasm of parasympathetic ganglion cells but only occasional fibres. In addition, GAD enzymatic activity was detectable in both sympathetic ganglia and vagus nerve. Incubation of sera or GAD-6 overnight with a crude homogenate of human brain as an antigen source abolished staining of the nervous tissues by GAD-6, but not by patients' sera. The different localisation of GAD and the autoantigens targeted by patients' sera indicates that GAD is not the target of the autoantibodies characteristic of DAN. Moreover, absorption studies using human brain homogenate suggest that the targets of anti-sympathetic ganglion and anti-vagus nerve autoantibodies are absent or represented only at low levels in the central nervous system and may be confined to the periphery.

Autoantibodies↗
PubMed1997

A 12-year-old girl with antimitochondrial antibody-positive autoimmune hepatitis.

Autoimmune hepatitis is rare and, in childhood, is typically associated with either the nuclear and/or smooth muscle antibody or with the liver kidney microsomal type 1 antibody. Antimitochondrial antibodies, which are considered diagnostic of primary biliary cirrhosis, have not been described in the paediatric age. We report for the first time a 12-year-old girl with antimitochondrial-antibody-positive autoimmune hepatitis. Antimitochondrial antibody positivity was determined by immunofluorescence and immunoblot. The patient's age, clinical, biochemical and histological features and response to immunosuppressive treatment support the diagnosis of autoimmune hepatitis.

Aspartate Aminotransferases↗
PubMed1997

Establishment of a novel radioligand assay using eukaryotically expressed cytochrome P4502D6 for the measurement of liver kidney microsomal type 1 antibody in patients with autoimmune hepatitis and hepatitis C virus infection.

BACKGROUND/AIMS: Liver kidney microsomal type 1 antibody (LKM1) is the diagnostic marker of autoimmune hepatitis (AIH) type 2 and is also found in patients with hepatitis C virus (HCV) infection. Cytochrome P4502D6 (CYP2D6) is the documented target antigen of LKM1 in AIH, but not in HCV infection. To compare the reactivity in the two conditions, we established a radioligand assay using eukaryotically expressed CYP2D6 as target. METHODS: A 1.2-kb human CYP2D6 cDNA was isolated from a human liver cDNA library and subcloned into an in vitro transcription vector pSP64 Poly(A). Recombinant CYP2D6 was then produced by in vitro transcription/translation, metabolically labelled with 35S methionine and used in the immunoprecipitation assay. Antibodies that bound radiolabelled CYP2D6 were immunoprecipitated and their levels assessed as cpm. Sera from 50 LKM1-positive patients (26 with AIH; 24 with HCV infection), 128 LKM1-negative patients and 57 normal controls were tested. RESULTS: Reactivity to 35S labelled CYP2D6 was observed in all LKM1-positive sera from patients with AIH and HCV infection, but in none of the controls. The cpm in both conditions were significantly higher than in normal controls (p<0.0001), and were correlated with the immunofluorescence titres of LKM1 (r 0.87, p<0.001 and r=0.64, p<0.001 for AIH and HCV infection, respectively). Reactivity to 35S labelled CYP2D6 was inhibited by addition of an excess of eukaryotically expressed CYP2D6. CONCLUSIONS: CYP2D6 is a major target antigen of both AIH and HCV infection. The novel radioligand assay is highly sensitive and specific.

Adolescent↗
PubMed1997

Autonomic nervous dysfunction in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA): possible pathogenic role of autoantibodies to autonomic nervous structures.

Autonomic nervous dysfunction has been previously reported in SLE, RA and systemic sclerosis, but the pathogenesis of such a complication is poorly understood. In the present study, four standard cardiovascular autonomic function tests were performed in 34 female patients with connective tissue diseases and in 25 healthy control subjects, and results expressed as cardiovascular (CV) test scores. Moreover, in each subject the presence of circulating complement-fixing autoantibodies directed against sympathetic and parasympathetic nervous structures, represented by superior cervical ganglia and vagus nerve, respectively, was simultaneously assessed by an indirect immunofluorescent complement-fixation technique, using rabbit tissue as substrate. None of the patients reported autonomic symptoms. However, an abnormal CV test score (> or = 5) was detected in 15% of the patients and in none of the healthy control subjects, approaching statistical significance (P = 0.07). No correlation was found between CV test results and disease duration, type of therapy or presence of conventional autoantibodies. One or two autoantibodies to autonomic nervous structures were detected in six patients (18%) and not in the control subjects (P < 0.05). Values of deep breathing test were significantly lower in autoantibody-positive patients compared with those amongst the control subjects (P < 0.05), and an abnormal CV test score was significantly associated with the presence of autoantibodies to autonomic nervous structures (P < 0.05). In conclusion, we confirm that autonomic nervous function can be impaired in patients with connective tissue diseases, and suggest that autoantibodies directed against autonomic nervous system structures may play a role in the pathogenesis of the autonomic dysfunction.

Adolescent↗
PubMed1997

Alcohol dehydrogenase: a target of humoral autoimmune response in liver disease.

BACKGROUND & AIMS: Liver-specific membrane lipoprotein (LSP) is a heterogeneous liver preparation that has been widely used to study autoreactivity in liver disease. The aim of this study was to identify autoantigens in LSP. METHODS: Guinea pig anti-LSP serum was used to screen a human liver complementary DNA (cDNA) library. Humoral immune responses to isolated potential autoantigens were investigated by immunoblotting in 91 pediatric patients with various liver diseases, 20 adult patients with alcoholic liver disease and 20 with autoimmune thyroid disease, 37 healthy children, and 20 healthy adults. RESULTS: A 1.6-kilobase cDNA insert isolated from the cDNA library was found to encode amino acids 61-374 of the human alcohol dehydrogenase (ADH)-gamma 1 subunit. Antibodies to this or other ADH subunits were found significantly more frequently in autoimmune liver diseases (19 of 39 patients; 49%), Wilson's disease (5 of 13 patients; 38%), and alcoholic liver disease (10 of 20 patients; 50%) than in normal controls (P < 0.0001, P < 0.005, and P < 0.05, respectively) and correlated with disease activity in autoimmune liver disease. CONCLUSIONS: ADH has been identified as a new antigenic component of the LSP using a xenogeneic antiserum to immunoprobe a human cDNA liver library and seems to be a target autoantigen in liver disease. This approach may be useful in identifying other potential autoantigens.

Adolescent↗
PubMed1996

Autoantibody prevalence in chronic hepatitis B virus infection: effect in interferon alfa.

The most effective treatment of chronic hepatitis B virus (HBV) infection is interferon alfa (IFN-alpha), a potentially severe side effect of which is the induction of autoimmunity. To assess whether IFN-alpha causes clinical or serological autoimmune manifestations, we studied 61 children randomized to receive 5 MU/m2 of IFN-alpha three times per week for 12 weeks, with or without steroid priming or no treatment. Autoantibodies to antinuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC), liver kidney microsomal type 1, mitochondrial, liver cytosolic antigen, thyroid microsomal, and thyroid globulin were detected by standard techniques. Over a median of 4 years (range, 1-5 years) from randomization, no clinical signs of autoimmunity were observed. Autoantibody positivity for nuclei, smooth muscle, and/or gastric parietal cells was observed on at least one occasion in 42 of 61 children (69%), with no overall difference in the prevalence between patients treated with interferon alone (19 of 24 [79%]), steroids plus interferon (13 of 20 [65%]), or untreated controls (10 of 17 [59%]). There was also no difference in the autoantibody prevalence before, during, and at follow-up after cessation of treatment in both interferon-treated and interferon-untreated patients. Autoantibodies are common in chronic HBV infection, and their prevalence is uninfluenced by IFN-alpha.

Adolescent↗